Biomedical subjects

Jiaqi Wu

Publications and source records attributed to Jiaqi Wu.

6 recordsLinked to original sources

PubMed2026

CAR T-cell therapy as a definitive consolidation for older adults with B-ALL in first complete remission.

We report a phase 1 study assessing the safety and efficacy of CD19 chimeric antigen receptor (CAR) T cells as definitive consolidation in older adults (aged ≥55 years) with B-cell acute lymphoblastic leukemia (B-ALL) in first complete remission (CR1). Eighteen patients received lymphodepletion followed by infusion of memory-enriched CD19 CAR T cells. The median age was 64 years, and all patients were measurable residual disease (MRD)-negative before lymphodepletion. There were no dose-limiting toxicities, grade ≥2 cytokine release syndrome, or any grade immune effector cell-associated neurotoxicity syndrome. Estimated 18-month event-free and overall survival were 84% and 100%, respectively. CAR T cells expanded in the blood and cerebrospinal fluid despite patients' MRD-negative status. Comparing clinical samples from patients with relapsed/refractory (R/R) B-ALL from our historical trial (ClinicalTrials.gov identifier: NCT02146924) and patients in CR1, we found that the blood and CAR T-cell products from patients with R/R B-ALL were hyperinflammatory and hyperimmunometabolic, respectively. First-line CAR T-cell therapy was safe and well tolerated and potentially extended remission in patients in MRD-negative CR1. These findings support further investigation of the early use of CAR T-cell therapy for B-ALL. This trial was registered at www.clinicaltrials.gov as NCT05707273.

Humans↗

PubMed2026

The complete sequence of the silkworm W chromosome uncovers its rapid evolution by large-scale duplications/deletions and translocation of W-linked genes.

The complete sequence of the W chromosome, which carries feminization activity in the silkworm, is crucial for understanding the sex-determination system in Lepidoptera. However, extensive accumulation of transposons due to lack of recombination, the very rare protein-coding genes and almost no information about molecular markers has hindered full W sequencing. We report the first complete silkworm W sequence (T2T_W, 11683305 bp) obtained by combining sequencing-assembly technologies and newly developed error detection methods, evaluated with genetically mapped W-RAPD markers, W-mutants, and W-derived BAC clones. The T2T_W sequence showed that the W is composed of a massive 92% accumulation of transposons and repeat sequences, among which the main constituents are intact LTR/LINE retrotransposons indicating recent expansions. In addition to Fem clusters producing Fem piRNA (Feminizer-derived PIWI-interacting RNA), we found 26 protein-coding genes in the W sequence. These include four gene pairs encoding zinc-finger motifs designated z1:z20 and a gene encoding serine/arginine repetitive matrix protein 1-like (SRRM1-like). To identify candidate genes for female sex-determination and differentiation we also sequenced the shortest W (3.8 Mb) from a translocation mutant with feminizing activity, which harbored four conventional genes: a Fem cluster, a pair of z1:z20 isoforms, z20-S, and a SRRM1-like gene. Phylogenetic analysis revealed that z1:z20 originated from a copy of an autosomal zinc-finger gene pair, z2:z21, translocated onto the W around 2.43 Mya and subsequently amplified to yield 4 W-linked zinc-finger gene pairs. The complete W sequence revealed that large-scale deletions and amplifications played a significant role in W chromosome evolution.

Animals↗

PubMed2026

Oral bacteriome in pediatric patients with malignancies prior to chemotherapy: a pilot study using full-length 16S rRNA sequencing.

OBJECTIVE: To characterize the composition, diversity, and ecological features of the oral bacteriome in pediatric patients with malignancies prior to chemotherapy initiation. METHODS: In this prospective pilot study,supragingival plaque samples were collected from 10 pediatric cancer patients prior to the initiation of chemotherapy. Bacterial genomic DNA was extracted from each sample, and the full-length 16S rRNA gene was amplified and sequenced on the PacBio Sequel II platform using circular consensus sequencing (CCS). Raw CCS reads were quality-filtered and denoised into amplicon sequence variants (ASVs) using DADA2, and taxonomic assignment was performed against the SILVA 138 reference database. Alpha diversity was assessed using the Chao1, Shannon, Simpson, and Faith's phylogenetic diversity (PD whole tree) indices, while beta diversity was evaluated through principal coordinate analysis (PCoA), and non-metric multidimensional scaling (NMDS). Microbial co-occurrence networks were constructed to characterize bacterial interactions, and functional potential was predicted using PICRUSt2, and BugBase. RESULTS: A total of 614,473 high-quality CCS reads were generated, yielding 1,697 ASVs. Alpha diversity analysis revealed substantial inter-individual variation in microbial richness and diversity among the pediatric cancer patients. The bacterial community was dominated by the phyla Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota. At the genus level, Streptococcus, Prevotella, Neisseria, and Haemophilus were the most abundant taxa. Beta diversity analysis revealed distinct clustering patterns, indicating highly individualized microbial profiles. Co-occurrence network analysis identified several keystone taxa and potential pathogenic associations within the supragingival plaque community. Functional prediction indicated that the dominant metabolic pathways were related to amino acid metabolism, carbohydrate metabolism, and membrane transport. CONCLUSION: These preliminary findings reveal a taxonomically diverse, highly individualized pre-chemotherapy oral bacteriome, providing foundational baseline profiles to guide future longitudinal investigations of chemotherapy-induced dysbiosis and personalized interventions.

Humans↗

PubMed2026

Inference of Genetic Structure and the Process of Population Formation in Nepalese Native Goats Using Uniparental and Genome-Wide Markers.

Nepal is a small, landlocked country with marked elevational variation from the Terai plains to the Himalayas. Here, four indigenous goat populations (Chyangra, Sinhal, Khari, and Terai) are raised at different elevations. This study aimed to clarify the genetic structure of these populations and how they are formed and propagated across the Himalayan region. We analyzed 136 Nepalese goats using mitochondrial (mt) DNA D-loop and sex-determining region Y (SRY) 3'-untranslated region (UTR) sequences, as well as 50 K SNP array data. The mtDNA haplogroups D (0.162) and G (0.03) were detected only in Chyangra, whereas haplogroup B was predominant in Sinhal (0.42), followed by Khari (0.260). Regarding SRY haplotypes, Y2B was detected in all populations, whereas Y1AB (0.42) was found only in Chyangra. Genome-wide SNP analysis showed that Chyangra was genetically related to Tibetan and Central Asian goats, while Terai resembled South Asian goats. Interestingly, Sinhal formed a distinct cluster, whereas Khari exhibited an admixed genetic structure. These findings suggest that Nepalese goats originate from at least three ancestral lineages and that an additional migration route may have existed through the southern Himalayas.

50K SNP↗

PubMed2026

Molecular evolution and immune expression analysis of ELF transcription factors in Lethenteron reissneri.

As important members of the ETS superfamily, the E74-like factor (ELF) transcription factor family regulates gene transcription through a conserved ETS domain and plays critical roles in immune regulation. However, the evolutionary characteristics and functions of this family in lampreys (Lethenteron reissneri) remain unclear. In this study, the ELF gene family of lampreys (Lr-ELF1, Lr-ELF2, Lr-ELF3, and Lr-ELF5) was systematically identified, and their molecular evolutionary features and immune response functions were investigated. Phylogenetic analysis revealed evolutionary characteristics reflecting the transition from jawless to jawed vertebrates. Domain architecture, gene structure, and three-dimensional structural analyses indicated that these genes appear to be conserved among vertebrates, with their three-dimensional structures showing high similarity to the core secondary structural elements of human homologous proteins. Synteny analysis demonstrated significant differences in the genomic neighborhoods of ELF genes between lampreys and jawed vertebrates. Quantitative real-time PCR (qRT-PCR) was performed with three biological and three technical replicates; relative expression levels were calculated using the ΔCt method, and statistical analysis was carried out with GraphPad Prism 9. Quantitative real-time PCR (qRT-PCR) results suggested that the ELF gene family may be involved in immune defense. This study not only enriches our understanding of the evolution of ELF genes but also provides new insights into the roles of lamprey ELFs in immune defense.

Animals↗

PubMed2026

A Phosphoproteomic Platform Identifies Erythrocyte Membrane Protein Band 4.1-Like 3-Mediated Lipid Droplet Remodeling Linked to Liver Cancer Invasion and Migration.

Aberrant lipid metabolism is a hallmark of hepatocellular carcinoma (HCC), yet the regulatory mechanisms governing lipid droplet (LD) dynamics and their contribution to tumor progression remain poorly understood. Here, we developed an ultrasensitive phosphoproteomic platform using high-affinity HPDA@Ti4+ nanospheres to map LD-associated phosphorylation events across six HCC cell lines. By correlating phosphoproteomic signatures with LD morphology, we identified distinct regulatory signatures associated with LD size and abundance. Functional perturbation screens identified two distinct phosphoprotein modules controlling LD size: silencing SH3KBP1, SLK, EHD2, EPB41L3, and NEXN reduced LD size in Huh1 cells, whereas silencing CPD, BET1, UFL1, RRP1B, OGFR, and CD2BP2 enlarged LDs in Huh7 cells. Notably, we identified EPB41L3 as a critical metabolic-metastatic link; its loss decreased LD size and accelerated HCC migration and invasion, correlating with poor clinical prognosis. Crucially, we identified five key phosphorylation sites on EPB41L3 essential for its function; substituting these with alanine completely abolished its regulatory control over both LD size and HCC metastatic potential. Together, these findings delineate a phosphorylation-based regulatory network controlling the LD architecture and metastatic potential in HCC. Our study not only identifies potential therapeutic targets but also establishes a generalizable phosphoproteomic framework for interrogating lipid signaling in cancer metabolism.

Humans↗